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|Title:||Quercetin relaxes rat tail main artery partly via a PKG-mediated stimulation of KCa1.1 channels||Authors:||Iozzi, Donata
Kalenchuk, V. U.
Sgaragli, GIAN PIETRO
|Issue Date:||2013||Project:||None||Journal:||ACTA PHYSIOLOGICA||Abstract:||
AIM: Protein kinases, activated by vasodilator substances, affect vascular function by regulating large conductance Ca(2+) -activated K(+) (KCa 1.1) channels. Thus, the aim of the present investigation was to address the hypothesis that quercetin-induced vasorelaxation is caused by a PKG-mediated stimulation of KCa 1.1 currents. METHODS: Single freshly isolated myocytes and endothelium-denuded rings of the rat tail main artery were employed for electrophysiological and contractility measurements respectively. RESULTS: Quercetin relaxed vessels and increased KCa 1.1 currents in a concentration-dependent manner: both effects were antagonized by the specific KCa 1.1 channel blocker iberiotoxin. Stimulation of KCa 1.1 currents was fully reversible upon drug washout, markedly reduced by Rp-8-Br-PET-cGMPs, a PKG-inhibitor, but not affected by catalase. Quercetin shifted by 34.3 mV the voltage dependence of KCa 1.1 channel activation towards more negative membrane potentials without affecting its slope. Under conditions of tight functional coupling between sarcoplasmic reticulum Ca(2+) release sites and KCa 1.1 channels, quercetin decreased both the frequency and the amplitude of KCa 1.1 transient currents in a ryanodine-like manner. CONCLUSION: The natural flavonoid quercetin relaxes the rat tail main artery partly via a PKG-mediated stimulation of smooth muscle KC a 1.1 channels.
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